Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.

BACKGROUND: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. METHODS: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. FINDINGS: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). INTERPRETATION: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. FUNDING: UK Medical Research Council and Health Technology Assessment Programme.

Editor's Choice - Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial.

OBJECTIVE: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. METHODS: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. RESULTS: The median follow up was 19.4 years (interquartile range 16.9 - 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 - 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). CONCLUSION: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.

Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials.

BACKGROUND AND PURPOSE: CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. METHODS: Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. RESULTS: Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. CONCLUSIONS: There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).

Development and Internal Validation of a Risk Score to Detect Asymptomatic Carotid Stenosis.

OBJECTIVE: Asymptomatic carotid stenosis (ACS) is associated with an increased risk of ischaemic stroke and myocardial infarction. Risk scores have been developed to detect individuals at high risk of ACS, thereby enabling targeted screening, but previous external validation showed scope for refinement of prediction by adding additional predictors. The aim of this study was to develop a novel risk score in a large contemporary screened population. METHODS: A prediction model was developed for moderate (≥50%) and severe (≥70%) ACS using data from 596 469 individuals who attended screening clinics. Variables that predicted the presence of ≥50% and ≥70% ACS independently were determined using multivariable logistic regression. Internal validation was performed using bootstrapping techniques. Discrimination was assessed using area under the receiver operating characteristic curves (AUROCs) and agreement between predicted and observed cases using calibration plots. RESULTS: Predictors of ≥50% and ≥70% ACS were age, sex, current smoking, diabetes mellitus, prior stroke/transient ischaemic attack, coronary artery disease, peripheral arterial disease, blood pressure, and blood lipids. Models discriminated between participants with and without ACS reliably, with an AUROC of 0.78 (95% confidence interval [CI] 0.77-0.78) for ≥ 50% ACS and 0.82 (95% CI 0.81-0.82) for ≥ 70% ACS. The number needed to screen in the highest decile of predicted risk to detect one case with ≥50% ACS was 13 and that of ≥70% ACS was 58. Targeted screening of the highest decile identified 41% of cases with ≥50% ACS and 51% with ≥70% ACS. CONCLUSION: The novel risk model predicted the prevalence of ACS reliably and performed better than previous models. Targeted screening among the highest decile of predicted risk identified around 40% of all cases with ≥50% ACS. Initiation or intensification of cardiovascular risk management in detected cases might help to reduce both carotid related ischaemic strokes and myocardial infarctions.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Procedural Risks of Carotid Intervention in 19,000 Patients.

BACKGROUND: Randomized controlled trials (RCTs) show that carotid endarterectomy (CEA) and carotid stenting (CAS) reduce long-term stroke risk in symptomatic and asymptomatic patients with carotid artery stenosis. Historical RCTs may not represent contemporary practice and administrative datasets may estimate procedural risks more reliably. We studied procedural risks after carotid intervention in a novel, international administrative data set of 18,997 patients admitted to 28 hospitals across 7 countries. METHODS: Symptomatic and asymptomatic patients undergoing CEA (n = 16,220) and CAS (n = 2,777) between 2011 and 2015 were studied retrospectively. The primary outcome was in-hospital death within seven days. The secondary outcome was the proportion of patients whose length of hospital stay (LOS) exceeded 2 days. We also describe the rate of computerized tomography brain imaging within 2 days of CEA and CAS (proxy for stroke) as procedural strokes were not reliably recorded. RESULTS: In symptomatic patients after CEA, mortality was 0.2% [5/2,118] (95% confidence interval: 0.1-0.5), and 57.0% [628/1,101] (54.1-60.0) had prolonged LOS. In asymptomatic patients after CEA, mortality was 0.1% [21/14,102] (0.1-0.2), and 28.5% [2,864/10,039] (27.7-29.4) had prolonged LOS. In symptomatic patients after CAS, mortality was 3.3% [10/307] (1.3-5.2), and 64.3% [144/224] (58.0-70.5) had prolonged LOS. In asymptomatic patients after CAS, mortality was 0.7% [18/2,470] (0.4-1.1), and 27.5% [601/2,187] (25.6-29.4) had prolonged LOS. After CEA, 8.1% [89/1,101] (6.5-9.7) symptomatic patients and 2.1% [207/10,039] (1.8-2.3) asymptomatic patients underwent brain imaging. After CAS, 7.1% [16/224] (4.0-10.7) symptomatic patients and 3.2% [71/2,187] (2.5-4.0) asymptomatic patients underwent brain imaging. CONCLUSIONS: Death and LOS after CEA and CAS were higher in symptomatic than asymptomatic patients. Symptomatic patients undergoing CAS had particularly increased risk of death. This may be partly explained by case selection, with more comorbid patients preferentially undergoing CAS. While RCTs effectively compare long-term efficacy of CEA versus CAS, administrative datasets can provide reliable estimates of contemporary procedural risks.

Improving Quality of Carotid Interventions: Identifying Hospital-Level Structural Factors that can Improve Outcomes.

BACKGROUND: "Structural factors" relating to organization of hospitals may affect procedural outcomes. This study's aim was to clarify associations between structural factors and outcomes after carotid endarterectomy (CEA) and carotid endarterectomy stenting (CAS). METHODS: A systematic review of studies published in English since 2005 was conducted. Structural factors assessed were as follows: population size served by the vascular department; number of hospital beds; availability of dedicated vascular beds; established clinical pathways; surgical intensive care unit (SICU) size; and specialty of surgeon/interventionalist. Primary outcomes were as follows: mortality; stroke; cardiac complications; length of hospital stay (LOS); and cost. RESULTS: There were 11 studies (n = 95,100 patients) included in this systematic review. For CEA, reduced mortality (P < 0.0001) and stroke rates (P = 0.001) were associated with vascular departments serving >75,000 people. Larger hospitals were associated with lower mortality, stroke rate, and cardiac events, compared with smaller hospitals (less than 130 beds). Provision of vascular beds after CEA was associated with lower mortality (P = 0.0008) and fewer cardiac events (P = 0.03). Adherence to established clinical pathways was associated with reduced stroke and cardiac event rates while reducing CEA costs. Large SICUs (≥7 beds) and dedicated intensivists were associated with decreased mortality after CEA while a large SICU was associated with reduced stroke rate (P = 0.001). Vascular surgeons performing CEA were associated with lower stroke rates and shorter LOS (P = 0.0001) than other specialists. CAS outcomes were not influenced by specialty but costless when performed by vascular surgeons (P < 0.0001). CONCLUSIONS: Structural factors affect CEA outcomes, but data on CAS were limited. These findings may inform reconfiguration of vascular services, reducing risks and costs associated with carotid interventions.

A systematic review and meta-analysis of complication rates after carotid procedures performed by different specialties.

OBJECTIVE: Different competencies and skills are required and obtained during medical specialization. However, whether these have an impact on procedural outcomes of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. We assessed the reported association between operator specialization and procedural outcomes after CEA or CAS to determine whether CEA and CAS should be performed by specific specialties. METHODS: We systematically searched PubMed and Embase up to August 21, 2017, for randomized clinical trials and observational studies that compared two or more specialties performing CEA or CAS for symptomatic and asymptomatic carotid artery stenosis. The composite primary outcome was procedural stroke or death (ie, occurring within 30 days of the procedure or before discharge). Risk estimates were pooled with a generic inverse variance random effects model. RESULTS: A total of 35 studies (26 providing data on CEA, 8 providing data on CAS, and 1 providing data on both CEA and CAS) were included, describing 256,033 CEA and 38,605 CAS procedures. For CEA, decreased risk of procedural stroke or death for operations performed by vascular surgeons was found with pooled unadjusted relative risk (RR) of 0.63 (95% confidence interval [CI], 0.46-0.86; seven studies) compared with neurosurgeons and RR of 0.81 (95% CI, 0.66-0.99; six studies) compared with general surgeons. An increased risk of procedural stroke or death for operations performed by neurosurgeons compared with cardiothoracic surgeons was found with a pooled unadjusted RR of 1.22 (95% CI, 1.02-1.46). No studies adjusted for potential confounding, and no significant unadjusted associations were found in other comparisons of operator specialty for the primary outcome. For CAS, no differences in procedural stroke or death were found by operator specialty. CONCLUSIONS: Studies were at high risk of bias mainly because of potential confounding by patient selection for CEA and CAS. Current evidence is insufficient to restrict CEA or CAS to specific specialties.

Management of carotid stenosis for primary and secondary prevention of stroke: state-of-the-art 2020: a critical review.

Carotid atherosclerotic plaque is encountered frequently in patients at high cardiovascular risk, especially in the elderly. When plaque reaches 50% of carotid lumen, it induces haemodynamically significant carotid stenosis, for which management is currently at a turning point. Improved control of blood pressure, smoking ban campaigns, and the widespread use of statins have reduced the risk of cerebral infarction to <1% per year. However, about 15% of strokes are still secondary to a carotid stenosis, which can potentially be detected by effective imaging techniques. For symptomatic carotid stenosis, current ESC guidelines put a threshold of 70% for formal indication for revascularization. A revascularization should be discussed for symptomatic stenosis over 50% and for asymptomatic carotid stenosis over 60%. This evaluation should be performed by ultrasound as a first-line examination. As a complement, computed tomography angiography (CTA) and/or magnetic resonance angiography are recommended for evaluating the extent and severity of extracranial carotid stenosis. In perspective, new high-risk markers are currently being developed using markers of plaque neovascularization, plaque inflammation, or plaque tissue stiffness. Medical management of patient with carotid stenosis is always warranted and applied to any patient with atheromatous lesions. Best medical therapy is based on cardiovascular risk factors correction, including lifestyle intervention and a pharmacological treatment. It is based on the tri-therapy strategy with antiplatelet, statins, and ACE inhibitors. The indications for carotid endarterectomy (CEA) and carotid artery stenting (CAS) are similar: for symptomatic patients (recent stroke or transient ischaemic attack ) if stenosis >50%; for asymptomatic patients: tight stenosis (>60%) and a perceived high long-term risk of stroke (determined mainly by imaging criteria). Choice of procedure may be influenced by anatomy (high stenosis, difficult CAS or CEA access, incomplete circle of Willis), prior illness or treatment (radiotherapy, other neck surgery), or patient risk (unable to lie flat, poor AHA assessment). In conclusion, neither systematic nor abandoned, the place of carotid revascularization must necessarily be limited to the plaques at highest risk, leaving a large place for optimized medical treatment as first line management. An evaluation of the value of performing endarterectomy on plaques considered to be at high risk is currently underway in the ACTRIS and CREST 2 studies. These studies, along with the next result of ACST-2 trial, will provide us a more precise strategy in case of carotid stenosis.

Associations of Perioperative Variables With the 30-Day Risk of Stroke or Death in Carotid Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- This analysis was performed to assess the association between perioperative and clinical variables and the 30-day risk of stroke or death after carotid endarterectomy for symptomatic carotid stenosis. Methods- Individual patient-level data from the 5 largest randomized controlled carotid trials were pooled in the Carotid Stenosis Trialists' Collaboration database. A total of 4181 patients who received carotid endarterectomy for symptomatic stenosis per protocol were included. Determinants of outcome included carotid endarterectomy technique, type of anesthesia, intraoperative neurophysiological monitoring, shunting, antiplatelet medication, and clinical variables. Stroke or death within 30 days after carotid endarterectomy was the primary outcome. Adjusted risk ratios (aRRs) were estimated in multilevel multivariable analyses using a Poisson regression model. Results- Mean age was 69.5±9.2 years (70.7% men). The 30-day stroke or death rate was 4.3%. In the multivariable regression analysis, local anesthesia was associated with a lower primary outcome rate (versus general anesthesia; aRR, 0.70 [95% CI, 0.50-0.99]). Shunting (aRR, 1.43 [95% CI, 1.05-1.95]), a contralateral high-grade carotid stenosis or occlusion (aRR, 1.58 [95% CI, 1.02-2.47]), and a more severe neurological deficit (mRS, 3-5 versus 0-2: aRR, 2.51 [95% CI, 1.30-4.83]) were associated with higher primary outcome rates. None of the other characteristics were significantly associated with the perioperative stroke or death risk. Conclusions- The current results indicate lower perioperative stroke or death rates in patients operated upon under local anesthesia, whereas a more severe neurological deficit and a contralateral high-grade carotid stenosis or occlusion were identified as potential risk factors. Despite a possible selection bias and patients not having been randomized, these findings might be useful to guide surgeons and anesthetists when treating patients with symptomatic carotid disease.

Safety of Carotid Revascularization in Patients With a History of Coronary Heart Disease.

Background and Purpose- We investigated whether procedural stroke or death risk of carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) is different in patients with and without history of coronary heart disease (CHD) and whether the treatment-specific impact of age differs. Methods- We combined individual patient data of 4754 patients with symptomatic carotid stenosis from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]). Procedural risk was defined as any stroke or death ≤30 days after treatment. We compared procedural risk between both treatments with Cox regression analysis, stratified by history of CHD and age (<70, 70-74, ≥75 years). History of CHD included myocardial infarction, angina, or coronary revascularization. Results- One thousand two hundred ninety-three (28%) patients had history of CHD. Procedural stroke or death risk was higher in patients with history of CHD. Procedural risk in patients treated with CAS compared with CEA was consistent in patients with history of CHD (8.3% versus 4.6%; hazard ratio [HR], 1.96; 95% CI, 0.67-5.73) and in those without (6.9% versus 3.6%; HR, 1.93; 95% CI, 1.40-2.65; Pinteraction=0.89). In patients with history of CHD, procedural risk was significantly higher after CAS compared with CEA in patients aged ≥75 (CAS-to-CEA HR, 2.78; 95% CI, 1.32-5.85), but not in patients aged <70 (HR, 1.71; 95% CI, 0.79-3.71) and 70 to 74 years (HR, 1.09; 95% CI, 0.45-2.65). In contrast, in patients without history of CHD, procedural risk after CAS was higher in patients aged 70 to 74 (HR, 3.62; 95% CI, 1.80-7.29) and ≥75 years (HR, 2.64; 95% CI, 1.52-4.59), but equal in patients aged <70 years (HR, 1.05; 95% CI, 0.63-1.73; 3-way Pinteraction=0.09). Conclusions- History of CHD does not modify procedural stroke or death risk of CAS compared with CEA. CAS might be as safe as CEA in patients with history of CHD aged <75 years, whereas for patients without history of CHD, risk after CAS compared with CEA was only equal in those aged <70 years.

High Operator and Hospital Volume Are Associated With a Decreased Risk of Death and Stroke After Carotid Revascularization: A Systematic Review and Meta-analysis.

OBJECTIVE: To examine the association between operator or hospital volume and procedural outcomes of carotid revascularization. BACKGROUND: Operator and hospital volume have been proposed as determinants of outcome after carotid endarterectomy (CEA) or carotid artery stenting (CAS). The magnitude and clinical relevance of this relationship are debated. METHODS: We systematically searched PubMed and EMBASE until August 21, 2017. The primary outcome was procedural (30 days, in-hospital, or perioperative) death or stroke. Obtained or estimated risk estimates were pooled with a generic inverse variance random-effects model. RESULTS: We included 87 studies. A decreased risk of death or stroke following CEA was found for high compared to low operator volume with a pooled adjusted odds ratio (OR) of 0.50 (95% confidence interval [CI] 0.28-0.87; 3 cohorts), and a pooled unadjusted relative risk (RR) of 0.59 (95% CI 0.42-0.83; 9 cohorts); for high compared to low hospital volume with a pooled adjusted OR of 0.62 (95% CI 0.42-0.90; 5 cohorts), and a pooled unadjusted RR of 0.68 (95% CI 0.51-0.92; 9 cohorts). A decreased risk of death or stroke after CAS was found for high compared to low operator volume with an adjusted OR of 0.43 (95% CI 0.20-0.95; 1 cohort), and an unadjusted RR of 0.50 (95% CI 0.32-0.79; 1 cohort); for high compared to low hospital volume with an adjusted OR of 0.46 (95% CI 0.26-0.80; 1 cohort), and no significant decreased risk in a pooled unadjusted RR of 0.72 (95% CI 0.49-1.06; 2 cohorts). CONCLUSIONS: We found a decreased risk of procedural death and stroke after CEA and CAS for high operator and high hospital volume, indicating that aiming for a high volume may help to reduce procedural complications. REGISTRATION: This systematic review has been registered in the international prospective registry of systematic reviews (PROSPERO): CRD42017051491.

Does metabolic syndrome influence short and long term durability of carotid endarterectomy and stenting?

AIMS: The metabolic syndrome (MetS) is composed of a cluster of related cardiovascular risk factors. The aim of the present study was to determine how MetS contributes to short- (30-day) and long-term complications and restenosis after carotid endarterectomy (CEA) or stenting (CAS). METHODS: A consecutive cohort of 752 patients undergoing CEA (n = 314) and CAS (n = 438) in a single institution was examined, of which 296 (39.4%) were identified as having MetS. All patients were followed-up with carotid duplex ultrasound scan of the supraaortic vessels and a neurological assessment of symptoms status at 30-day postprocedure and at 3, 6, and 12 months, with annual follow-up thereafter for 3 years. RESULTS: Patients with MetS had a significant increased risk in their 30-day death, major adverse events (MAE), and restenosis rates, both after CEA and after CAS (death: 0.7% vs 0.0%; MAE: 5.3% vs 2.7%; and restenosis: 1.7% vs 0.2%; p < 0.05). The MAE and restenosis rates remained statistically different at 36 months, with both procedures (29.2% vs 24.2% and 9.5% vs 3.3%, p < 0.05, for patients with and without MetS, respectively). Among the components of MetS, high fasting serum glucose, low high-density lipoprotein cholesterol, and elevated body mass index were associated with increased risk of complications at 30 days and within 36 months. CONCLUSIONS: The current study suggested that the presence of MetS is an important risk factor for morbidity and restenosis after CEA and CAS.

Optimal Antiplatelet Therapy in Moderate to Severe Asymptomatic and Symptomatic Carotid Stenosis: A Comprehensive Review of the Literature.

OBJECTIVES: Carotid stenosis patients are at risk of vascular events despite antiplatelet therapy. Data on prescribed antiplatelet regimens have not been comprehensively collated from trials to guide optimal therapy in this population. METHODS: This review was conducted in line with the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, Ovid, Embase, Web of Science, and Google Scholar from 1988 to 2018 were searched using the search terms "carotid stenosis", "asymptomatic", "symptomatic", "antiplatelet", and "anti-platelet" to identify randomised trials in patients with asymptomatic or symptomatic extracranial moderate-severe carotid stenosis on any form of antiplatelet therapy in which vascular events and pre specified composite outcome events were reported. RESULTS: Twenty-five studies were judged eligible for inclusion. Data from one randomised controlled trial showed no significant difference in benefit with aspirin versus placebo in asymptomatic carotid stenosis, but it is still reasonable to recommend aspirin (81-325 mg daily) for prevention of vascular events in these patients. Low to medium dose aspirin (81-325 mg daily) is superior to higher doses (>650 mg daily) at preventing recurrent vascular events in patients undergoing endarterectomy. Data from endovascular treatment (EVT) trials support peri-procedural treatment of asymptomatic and symptomatic patients with 81-325 mg of aspirin daily. The use of peri-procedural aspirin-clopidogrel in patients undergoing EVT is based on one pilot trial, but appears safe. Short-term aspirin-dipyridamole or aspirin-clopidogrel treatments are equally effective at reducing micro-embolic signals on transcranial Doppler ultrasound in patients with ≥50% symptomatic carotid stenosis. There is insufficient evidence to recommend routine aspirin-clopidogrel combination therapy to reduce the risk of recurrent clinical ischaemic events in patients with symptomatic moderate-severe carotid stenosis. CONCLUSIONS: This comprehensive review outlines an evidence based approach to antiplatelet therapy in carotid stenosis patients. Future trials should randomise such patients to receive different antiplatelet regimens to assess their efficacy and safety and to optimise peri-procedural and long-term preventive treatment in this patient cohort.

Immediate and Delayed Procedural Stroke or Death in Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- Stenting for symptomatic carotid stenosis (carotid artery stenting [CAS]) carries a higher risk of procedural stroke or death than carotid endarterectomy (CEA). It is unclear whether this extra risk is present both on the day of procedure and within 1 to 30 days thereafter and whether clinical risk factors differ between these periods. Methods- We analyzed the risk of stroke or death occurring on the day of procedure (immediate procedural events) and within 1 to 30 days thereafter (delayed procedural events) in 4597 individual patients with symptomatic carotid stenosis who underwent CAS (n=2326) or CEA (n=2271) in 4 randomized trials. Results- Compared with CEA, patients treated with CAS were at greater risk for immediate procedural events (110 versus 42; 4.7% versus 1.9%; odds ratio, 2.6; 95% CI, 1.9-3.8) but not for delayed procedural events (59 versus 46; 2.5% versus 2.0%; odds ratio, 1.3; 95% CI, 0.9-1.9; interaction P=0.006). In patients treated with CAS, age increased the risk for both immediate and delayed events while qualifying event severity only increased the risk of delayed events. In patients treated with CEA, we found no risk factors for immediate events while a higher level of disability at baseline and known history of hypertension were associated with delayed procedural events. Conclusions- The increased procedural stroke or death risk associated with CAS compared with CEA was caused by an excess of events occurring on the day of procedure. This finding demonstrates the need to enhance the procedural safety of CAS by technical improvements of the procedure and increased operator skill. Higher age increased the risk for both immediate and delayed procedural events in CAS, mechanisms of which remain to be elucidated. Clinical Trial Registration- URL: https://clinicaltrials.gov . Unique identifier: NCT00190398. URL: http://www.isrctn.com . Unique identifier: ISRCTN57874028. URL: http://www.isrctn.com . Unique identifier: ISRCTN25337470. URL: https://clinicaltrials.gov . Unique identifier: NCT00004732.

Prediction Models for Clinical Outcome After a Carotid Revascularization Procedure.

Background and Purpose- Prediction models may help physicians to stratify patients with high and low risk for periprocedural complications or long-term stroke risk after carotid artery stenting or carotid endarterectomy. We aimed to evaluate external performance of previously published prediction models for short- and long-term outcome after carotid revascularization in patients with symptomatic carotid artery stenosis. Methods- From a literature review, we selected all prediction models that used only readily available patient characteristics known before procedure initiation. Follow-up data from 2184 carotid artery stenting and 2261 carotid endarterectomy patients from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]) were used to validate 23 short-term outcome models to estimate stroke or death risk ≤30 days after the procedure and the original outcome measure for which the model was developed. Additionally, we validated 7 long-term outcome models for the original outcome measure. Predictive performance of the models was assessed with C statistics and calibration plots. Results- Stroke or death ≤30 days after the procedure occurred in 158 (7.2%) patients after carotid artery stenting and in 84 (3.7%) patients after carotid endarterectomy. Most models for short-term outcome after carotid artery stenting (n=4) or carotid endarterectomy (n=19) had poor discriminative performance (C statistics ranging from 0.49-0.64) and poor calibration with small absolute risk differences between the lowest and highest risk groups and overestimation of risk in the highest risk groups. Long-term outcome models (n=7) had a slightly better performance with C statistics ranging from 0.59 to 0.67 and reasonable calibration. Conclusions- Current models did not reliably predict outcome after carotid revascularization in a trial population of patients with symptomatic carotid stenosis. In particular, prediction of short-term outcome seemed to be difficult. Further external validation of existing prediction models or development of new prediction models is needed before such models can be used to support treatment decisions in individual patients.